After abdominal surgery, normal intestinal movement function may not routinely recover in 24 hours due to both trauma and anesthesia (causing early-stage postoperative enteroparalysis or ileus). The intestinal function will be affected by one or more of: irritation, effusion of abdominal cavity, inflammation and anesthesia effect, which cause intestinal distension and synechia. The later is the main cause of ileus.
It has been reported that the incidence rate of intestinal synechia is as high as 60-70% in all abdominal surgery, 5% of which develop intestinal ileus. The recurrence rate of ileus is high (over 15%) after synechia lysis. Indeed, the more operations, the higher the recurrence rate. [Editor: Chen Qi, Thoughts and Methods in Study on Medicinal Effectiveness of Chinese Medicine, People's Medical Publishing House p. 491-492, 2005].
The current treatments for intestinal distension and synechia in the clinic are Neostigmine injection or oral-administration of different “purgative” TCM formulas.
Although Neostigmine injection has good effect, and there are no restraints on its use, it has been reported that it could cause significant side effects, e.g. intestinal colic, increased gland secretion and muscle vibration. [Jiang M X and Yang Z C: Medical Pharmacology, People's Medical Publishing House, 3rd ed. Beijing, 1997, p 116].
The alternative, oral-administration of TCM formulas, also has some disadvantages, e.g. large volumes are difficult to take, and are not traditionally recommended immediately post operatively (postoperative patients should be fasted until flatus occurs and flatus is a sign of recovering gastrointestinal function). It has however been reported that the earlier the use of TCM formula after surgery, the better the therapeutic results could be. [Ma G X and Hou B Z: Clinical analysis on 405 cases of postoperative intestinal distension with Pai Qi Decoction, Chinese Medicine of Factory and Mine, 2002, 15(1): p 72-73].
Kudingxiang (Muskmelon-Base) is the dried fruit stem of Cucumis melo L. (Cucurbitaceae family). The functions and indications of Muskmelon-Base (Kudingxiang) described in the Chinese Materia Medica (Vol. V. pp. 4580) and Inner Mongolia Standard for Materia Medica (1988, pp. 64) are:
Inducing vomiting and diuresis,
Expelling dampness and reducing jaundice.
It is used to treat:
Stroke,
Epilepsy,
Sore throat,
Phlegmatic hygrosis choking,
Shortness of breath,
Dyspepsia,
Abdominal fullness, and
Damp-heat type of jaundice in TCM terms.
It is regarded as an emetic herb in the TCM system due to its stimulating action upon the gastric mucosa and its reflex triggering of the central vomiting nerve.
Cucurbitacins are the main chemical substances in Muskmelon Base. It has been reported in the journal of Chinese Traditional and Herbal Drugs (Vol. 23, No. 11, 1992) that Cucurbitacins have cytotoxicity and anti-tumour activity, offer hepatic protection, anti-hepatitis, improvement of immune function, anti-chemocarcinogenesis, an increase of capillary permeability, and induced vomiting.
A product made from Muskmelon Base, and currently sold in the Chinese markets, is “Hu Lu Su” tablet (meaning Cucurbitacins tablet). The product specification was recorded in the ‘Standard Specification of Traditional Chinese Medicines (Vol. 19)’ issued by the Ministry of Health, China.
The tablets comprise a purified ethanol extract of the raw material of Muskmelon Base and the main chemical in the tablet is Cucurbitacin B, the content of which is no less than 60% as stated in the above Standard Specification. The functions and indications for the tablet include:
Eliminating toxins and clearing heat, and
Inducing diuresis and expelling jaundice
and it is used as an adjunct treatment for persistent hepatitis due to severe toxic heat, chronic hepatitis and primary hepatic carcinoma.
Muskmelon Base did not have the function of ‘purgation’ in TCM but Edery et al, reported that intravenous injection of Cucurbitacin D isolated from Ecballium elaterium L. induced diarrhea in conscious cats and dogs, and also stimulated enterokinesia in anesthetized dogs. But on the isolated guinea pig ileum, a concentration of 54 mg/ml Cucurbitacin D did not cause any visible effect. [H. Edery, G. Schatzberg Porath, S. Gitter, Pharmacodynamic activity of Elatericin (Cucurbitacin D) Arch Int Pharmacodyn. 1961, 13(3˜4):315˜335].
It is an aim of the present invention to develop a medicament which will prevent intestinal distension and synechia and speed up gastroenterokinesia restoration. Such a medicament will have a significant impact on a patient's recovery after surgery.
The applicant has developed a standardized extract comprising Cucurbitacin D from Cucumis melo L and used this to develop a formulation for rectal delivery which has proved effective in animal studies.
The extract may be used alone or in combination with the other botanical ingredients or chemical substances to form the pharmaceutical preparation.
Furthermore the formulation avoids the hepatic by-pass effect associated with oral forms, is quick acting and would appear to benefit from no obvious muscle spasm side effect, a problem with Neostigmine the current preferred treatment.